In bioprocesses, such as during the development and manufacture of biologics and biosimilars, it is often necessary to monitor protein concentration (e.g., measurement of the protein titer) during the course of a production run to ensure product quality and maximize the yield of that production run. Typically, a production run is currently run as a batch process in a bio-reactor vessel (sometimes referred to as a bioreactor). In such production runs, the protein concentration versus time usually can be modeled as an exponential growth followed by a decay curve. The closer the manufacturer can come to ending the production run at this inflection point, the more efficient the production run and the subsequent steps in the process can be. Monitoring protein concentration can be a critical parameter in monitoring the production run. Given that a single batch of protein can be worth millions of dollars, it is critical that this growth is monitored in order to maximize the yield of each production run.
In such bioprocesses, samples are typically taken at the bio-reactor vessel and then moved to an onsite quality control lab for testing and analysis. A typical QC lab at a bioprocess facility is located in a different room than the bio-reactor vessel and has a backlog of samples for analysis. In addition, it is often a separate group within a given organization that will be performing the analysis. Often, the backlog of samples for testing is such that the analysis of a sample may not be completed for one or two days or so after the sample was taken. This situation creates a challenge for the manufacturers as they may be making decisions with respect to the production run based on old data. Furthermore, this approach and lab system typically requires a highly skilled individual (usually someone with a graduate level degree or perhaps a bachelor's degree with several years of relevant experience) to perform the analysis.
Once a production run in such a bioprocess is complete, a changeover step is usually required next, during which the manufacturing equipment is thoroughly cleaned and prepared for the next production run. Because the production of biologics and biosimilars is usually a very sensitive process, small amounts of any contamination can cause an entire production run to be scrapped, thereby resulting in a loss of potentially millions of dollars to the manufacturer. To ensure cleanliness, time consuming cleaning steps are typically written into manufacturer standard operating procedures. Any manufacturing or equipment component that comes into contact with the product must be thoroughly cleaned. Due to the risks and costs of any contamination, in addition to the cost of cleaning, and the time required for such cleaning, disposable devices (sometimes referred to as single use devices) have been increasingly considered for use in the industry. In addition, as the bioprocess industry matures, there has been a shift in the skill level of many production personnel, with the result that many processes and activities previously done by individuals with extensive skill and advanced degrees are in many situations done today by less educated technicians.
Conventional approaches have included various apparatus and methods for bioprocesses, which include US published patent application No. 2012/0138173 A1, entitled “Device For A Biological Liquid Treatment Installation”, with named inventors Sebastien Cirou, Rene Reinbigler, Virginie Buisson, Jean-Louis Weissenbach, which was published on Jun. 7, 2012 and describes a device comprising a base (2) and a door (20), said device having a closed door position in which a circuit (8) of the device comprises a bag comprising two flexible films and connectors of the conveying network, and a press (9) comprising a first shell (16) disposed on a front face (5) of said base (2) and a second shell (17) disposed in said door (20); and a hinge system hinging said door (20) relative to said base (2), and disposed only on one side of said door (20) so as to form lateral clearances between said door (20) and said base (2) over the rest of a perimeter of said door (20).
In U.S. Pat. No. 7,217,367 B2, entitled “Microfluidic chromatography,” issued to Jiang Huang, Hou-Pu Chou, and Marc A. Unger on May 15, 2007, a microfluidic chromatography apparatus is disclosed which comprises a microfabricated fluid delivery system and a chromatography column which is in fluid communication with the fluid delivery system, and a method for producing and using the same.
A disposable fluid path is described in U.S. Pat. No. 8,512,566 B2, entitled “Disposable fluid path systems and methods for processing complex biological materials,” issued to Weston Blaine Griffin, Jaydeep Roy, Eric Douglas Williams, Phillip Alexander Shoemaker, and James Mitchell White on Aug. 20, 2013. This patent describes a disposable fluid path for processing complex materials that comprises a gravity assisted disposable system for separating a biological sample into two or more distinct submaterials through sedimentation. The fluid path is comprised of a sample delivery conduit and bag-set wherein the bag set comprising a tubing assembly, a separation assembly, and a filter assembly. Methods of using the system are also disclosed.
A fluid sampling device is disclosed in US published patent application no. 2006/0201263 A1, entitled “Disposable, pre-sterilized fluid receptacle sampling device,” with named inventors James Furey, and Stephen Proulx, published on Sep. 4, 2006. In this patent application, a fluid sampling device comprising a port insert, a plurality of flexible conduits, and a plurality of sample containers is described, with the port insert having a body having a plurality of shafts therethrough and a rotatably displaceable member for individually opening and closing any of said shafts to enable the flow of fluid there through. Flexible conduits (e.g., flexible tubing) are equal in number to the shafts, with each flexible conduit connected to or otherwise in fluid communication with an individual shaft. Similarly, sample containers (e.g., flexible bags) are equal in number to the conduits, with each sample container connected to an individual conduit opposite the connection to the shaft. A specific configuration for the port insert, as well as kit containing sterilized components of the fluid sampling device, is also described.
U.S. Pat. Nos. 8,512,566 and 7,217,367, and United States published patent application nos. 2012/0138173 and 2006/0201263, are hereby incorporated by reference as if fully set forth herein.